The overall objective of this research is to analyze the roles of membrane deterioration, lipid peroxidation and free radical reactions as causes of cellular senescence and death, employing primarily the fungus Neurospora crassa as a model. Our hypothesis predicts that these inter-related processes are sources of molecular errors which are universal to the aging process. Nuclear mutants are used to induce premature senescence in growth rate and cellular viability. Premature senescence of wild-type N. crassa is induced by culture with amino acid analogs or by biotin starvation. Senescence in all model systems is partially alleviated by either antioxidants (free radical scavengers) or by various drugs that stabilize cellular membranes. BIBLIOGRAPHIC REFERENCES: K.D. Munkres and M. Minssen, Ageing of Neurospora crassa I. Evidence for the free radical theory of ageing from studies of a natural-death mutant, Mech. Ageing Develop., 5 (1976) 79-98. K.D. Munkres and H.J. Colvin, Ageing of Neurospora crassa, II. Organic hydroperoxide toxicity and the protective role of antioxidant and the antioxygenic enzymes, Mech. Ageing Develop., 5 (1976) 99-107.